Hyperfunction of Muscarinic Receptor Maintains Long-Term Memory in 5-HT4 Receptor Knock-Out Mice
PLoS ONE. 2010-03-04; 5(3): e9529
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1. PLoS One. 2010 Mar 4;5(3):e9529. doi: 10.1371/journal.pone.0009529.
Hyperfunction of muscarinic receptor maintains long-term memory in 5-HT4 receptor
Segu L(1), Lecomte MJ, Wolff M, Santamaria J, Hen R, Dumuis A, Berrard S,
Bockaert J, Buhot MC, Compan V.
(1)Centre de Neurosciences Intégratives et Cognitives, CNRS UMR5228, Bordeaux
University, Talence, France.
Patients suffering from dementia of Alzheimer’s type express less serotonin 4
receptors (5-HTR(4)), but whether an absence of these receptors modifies learning
and memory is unexplored. In the spatial version of the Morris water maze, we
show that 5-HTR(4) knock-out (KO) and wild-type (WT) mice performed similarly for
spatial learning, short- and long-term retention. Since 5-HTR(4) control mnesic
abilities, we tested whether cholinergic system had circumvented the absence of
5-HTR(4). Inactivating muscarinic receptor with scopolamine, at an ineffective
dose (0.8 mg/kg) to alter memory in WT mice, decreased long-term but not
short-term memory of 5-HTR(4) KO mice. Other changes included decreases in the
activity of choline acetyltransferase (ChAT), the required enzyme for
acetylcholine synthesis, in the septum and the dorsal hippocampus in 5-HTR(4) KO
under baseline conditions. Training- and scopolamine-induced increase and
decrease, respectively in ChAT activity in the septum in WT mice were not
detected in the 5-HTR(4) KO animals. Findings suggest that adaptive changes in
cholinergic systems may circumvent the absence of 5-HTR(4) to maintain long-term
memory under baseline conditions. In contrast, despite adaptive mechanisms, the
absence of 5-HTR(4) aggravates scopolamine-induced memory impairments. The
mechanisms whereby 5-HTR(4) mediate a tonic influence on ChAT activity and
muscarinic receptors remain to be determined.
PMID: 20209108 [Indexed for MEDLINE]